Stent Crimping Methods

ABSTRACT

A process for crimping stents includes a multi-stage process producing a desired stent retention and crimped profile in a reduced amount of time. The process achieves results by utilizing particular combinations of heat and pressure during the crimping process, which was found to produce the desired results.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to drug-eluting medical devices; moreparticularly, this invention relates to processes for crimping a stentto a delivery balloon.

2. Background of the Invention

A known stent retention process consists of three operations, stentcrimp, split mold and stent press. Stent crimp is the process by whichthe stent is placed on the catheter. First the stent is placed on apre-crimp mandrel and placed in the crimp machine. The crimp machinecloses onto the stent applying radial force causing the scent's diameterto be reduced to that of the pre-crimp mandrel. The pre-crimp mandreldiameter is selected based on the delivery systems folded balloonprofile. After pre-crimp, the stent is removed from the mandrel andplaced on a balloon delivery system, balloon catheter, or deliverysystem. The balloon catheter is placed into the crimp machine and radialforce applied to reduce the diameter of the stent onto the ballooncatheter. No heat or catheter inflation pressure is applied during thisoperation.

The delivery system now with the stent in place on the balloon is sentto the split mold operation. The split mold operation applies heat andpressurizes the delivery system for a specified amount of time to aspecified increased diameter causing the balloon to “pillow” between thestent struts, which further increases mechanical interaction betweenballoon and stent. The delivery system is then moved to a stent presswhere the stent and balloon are placed into a press machine and radialforce again applied to reduce the profile to a specified diameter,thereby again increasing the mechanical interaction between balloon andstent.

Related devices are mentioned in U.S. Pat. No. 7,763,198 ('198 patent)which is commonly owned with the present application. An example of the“split mold” is depicted in FIGS. 1-3 of the '198 patent. The bore ofthe split mold is machined within the block that forms the body of themold, with the two halves of the mold in place together during themachining. The diameter of the mold bore (FIG. 12) may be slightlylarger than the outer diameter of a crimped stent on the balloon of ethballoon catheter, or matched to that diameter, so that the stent doesnot radially expand during the stent mounting. The balloon is heated byheating the mold with via a conductive heating element member in theform of metal platens.

With the balloon catheter in position within the bore of the split mold,the mold is heated to an elevated temperature sufficient to soften theballoon but lower than the thermal limit of the drug disposed on or inthe stent. The mold is heated to a temperature of about 160° F. to about190° F., with the balloon catheter therein during the stent mountingprocedure, to soften a balloon formed of polymeric material. The '198patent shows a transverse cross section of the balloon catheter withstent gaps partially filled by balloon material so that the balloonmaterial contacts and partially encapsulates the side surfaces of thestent struts, to mount the stent on the balloon.

According to the '198 patent, during the initial, or pre-crimping and/orre-crimping process, i.e., before and after, respectively, thesplit-mold process the balloon may be pressurized and heated to increasethe protrusion of balloon material into the openings in the stentpattern, thereby further increasing stent retention on the balloon. Theballoon may be pressurized in the range of 10 to 300 pounds per squareinch (psi). The balloon may be heated to the range of about 70 degreesto 250 degrees Fahrenheit (21 to 121 degrees Celsius) duringre-crimping. The mounted stent can be heated to about 130 degreesFahrenheit (54 degrees Celsius) during re-crimping. The balloon may bepressurized to about 70 psi.

The '198 patent discloses various combinations of crimping, balloonpressure and heating of stent and balloon to reduce the stent profileand increase the retention of stent to balloon. However, the pre-crimp,split-mold and re-crimp phases of the process are performed separatelyusing separate machines. This process is time-consuming and does notyield an optimal combination of profile and dislodgment or retentionforce of the balloon and stent. Dislodgment or retention force means theforce needed to pull or dislodge the stent from the balloon. Furtherdetails on the meaning of dislodgment force or stent retention force maybe found in U.S. application Ser. No. 11/938,127 (Attorney Docket No.62571.266). What is needed is a process that simplifies the process ofcrimping a stent to a balloon, while also achieving the desired crimpedstent profile and increasing the dislodgment force. Accordingly, thereis a continuing need to improve upon the crimping methods for stents.

SUMMARY OF THE INVENTION

The invention provides a process and apparatus for crimping a stent to aballoon that reduces the processing time, involves fewer steps andproduces an increased dislodgment force for a stent crimped to aballoon. Prior processes for crimping a stent to a balloon have involveda pre-crimp process, followed by a balloon pressurization step within amold. This step was then followed by a final crimp stage where the stentis crimped to a final diameter. This process is time consuming andrequires the use of multiple machines for performing the process.Moreover, the dislodgment force was in need of improvement to facilitatebetter retention of the stent on the balloon during delivery to a targetsite in a vessel.

It was discovered, unexpectedly, that when parameters of the crimpingprocess are varied in a particular manner, the same retention and targetouter diameter profile for the catheter could be achieved withoutreducing yield, i.e., no increased rate of stent or balloon damage for abatch run using the new process and dislodgment force may be increasedwithout introducing other undesired qualities. In tests conducted usingthe new process the processing time could be reduced by about 70%,without reducing yield and with increased dislodgment force for thecrimped stent and balloon.

Accordingly, the advantages of the process according to the inventionmay be described as two-fold: a significant reduction in the duration ofa crimping process, primarily by a reduction in the dwell time duringpre-crimp, encapsulation, and final crimp; and increased dislodgmentforce without effecting the stent profile or deliverability of the stentthrough a tortuous pathway.

The process may be described as having three stages, which may proceedin a more or less continuous manner. Stage 1 is a pre-crimp stage. Thestent is loaded onto a mandrel and placed in a crimping machine where aniris type mechanism closes crimping jaws or blades onto the stent andreduces the profile of the stent down to a specified dimension. In Stage2, the stent is loaded onto the balloon catheter delivery system andplaced back into the crimping machine where the iris type mechanismcloses down to a specified dimension, the catheter is pressurized andthe distal end of the delivery system is heated for a specific amount oftime to cause pillowing of the balloon between stent struts. In Stage 3,the iris type mechanism may then open and closes to specified dimensionsto decreasing the stent dimension or profile, which causes increasedmechanical interaction between balloon and stent. Opening and closingthe iris type mechanism onto the stent several times may be performed inorder to work the stent material, to reduce recoil, decrease systemprofile and further increase the mechanical interaction between balloonand stent.

In an alternate embodiment of Stage 3, the iris-type mechanism does notincrease in diameter. Rather, the iris-type mechanism closes from theStage 2 iris diameter to a smaller, Stage 3 diameter. This Stage 3diameter may be less than the final crimp diameter. Catheterpressurization may also be added to Stage 3 processing to helpretain/increase the pillowing at the smaller dimension, thereby furtherincreasing the mechanical interaction between balloon and stent. Addingcatheter pressurization prior to or during the iris type mechanismreaching the final specified dimension or profile may also increase themechanical interaction between balloon and stent above just pressurizingthe system at the specified dimension for the specified dwell time. Bypressurizing during the closing of the iris, for example, the stent andballoon position is fixed or constrained relative to each other, whichallows for an existing imprint of the stent on the balloon (formedduring stage 2) to be substantially retained or unaltered when the stentis reduced in diameter, which increases the mechanical interaction.

The setting ranges for a crimping process may include a temperature of110° F.-250° F. The upper range for temperature may be defined in termsof the material characteristics of the coating material. For example, ifa drug-polymer coating is particularly sensitive to temperatureincreases the upper temperature range may be limited by the drug-polymercoating. Alternatively, the lower range of this temperature, may,according to some embodiments, be defined by the lower limit of theglass transition temperature for the balloon material, the lower glasstransition temperature for the co-block polymer PEBAX. It is alsobelieved that the temperature may, in some embodiments, be reduced toabout room temperature if the balloon pressure is high enough during thecrimping process.

Dwell times at a processing stage may range between about 1 sec. to 90sec., a crimped diameter for the stent ranging from about 0.018″ to0.400″ and catheter pressurization during Stages 1-3 being between 50psi and 400 psi. The number of Stage 3 iterations may range from 1 to 8,in which each cycle includes a diameter reduction, balloonpressurization and dwell time to increase stent retention and arrive atthe desired final crimp diameter. In other embodiments the number ofStage 3 iterations may be higher than 8, e.g., to work material toreduce recoil and/or increase the dislodgment force further. In apreferred embodiment the process parameters are

Temperature: 170° F.;

Stage 1, 2 and 3 dwell times: 1 seconds, 30 seconds, and 3 seconds,respectively;

Stent diameters at the conclusion of Stages 1, 2 and 3 are,respectively, 0.0336″, 0.052″, and 0.040″;

Maximum catheter pressurization at each stage: 300 psi; and

Number of Stage 3 iterations: 1 to 6

In accordance with the foregoing objectives, the invention provides, inone embodiment a method for crimping a stent to a balloon including thesteps of i. elevating the temperature of the stent; ii. pre-crimping thestent including reducing the stent diameter to a first diameter, whereinthe stent has a first elevated temperature while the diameter is beingreduced to the first diameter; iii. removing the stent from the crimphead following the pre-crimping step and placing the stent on a ballooncatheter to assemble a stent-catheter assembly, a balloon of the ballooncatheter capable of being pressurized through a proximal end of aninflation lumen of the balloon catheter; iv. placing the stent-catheterassembly within the crimp head and increasing the stent temperature to asecond elevated temperature, while the stent has the second elevatedtemperature, pressurizing the balloon via the inflation lumen while thestent-catheter assembly is within the crimp head; following step iv,pressing the stent into the balloon, the stent having a third elevatedtemperature, step v including reducing the stent diameter using thecrimp head from about the second diameter to about the final crimpdiameter while maintaining the balloon pressure; and removing thestent-catheter assembly from the crimp head.

In some embodiment, prior to removal of the stent-catheter assembly fromthe crimp head a leak test may be performed on the stent-catheter tocheck for any leaks or damage to the balloon. A leak test raises balloonpressure to a specified amount, e.g., 150 psi, then monitors balloonpressure to see whether the pressure changes over a specified dwellperiod, e.g., 1-2 minutes. In other embodiments the leak test may beperformed outside of the crimp head, such as when it is desirable tohave the leak test performed at body or room temperature (for batchprocesses with the crimp blades at an elevated temperature it may bepreferable, therefore, to have the leak test done outside the crimp headso that a constant crimp head temperature can be maintained throughoutthe batch process).

Step iv may include placing a sheath having an inner diameter of about25% greater than the stent first diameter over the stent to protect acoating on the stent, wherein the sheath has a radial stiffness suchthat the presence of the sheath over the stent provides the up to about25-30% of the first diameter restraint on stent expansion during stepiv. This range may be increased and the sheath may be further aided bythe crimper blades to provide a restraint on stent expansion tofacilitate the interlocking of balloon material with stent struts.

The pressing the stent into balloon step (step v) may include having thestent reduced by up to about 40% in diameter while simultaneously havingthe stent maintain an elevated temperature and balloon pressure beingapplied, e.g., about 150-300 psi. In a preferred embodiment pressure andtemperature is maintained from the prior art during the up to 40%diameter reduction. It has been found that there is a significantincrease in dislodgment force, far more than would have been expected,when pressure and temperature are maintained during this diameterreduction. In one embodiment the up to 40% reduction moves the stentdiameter to less than the final crimp diameter followed by a threesecond dwell. Additionally, the stent and balloon are then furthercycled including repeatedly applying then withdrawing the crimp head andadjusting balloon pressure to further increase dislodgment force.

According to another embodiment, a method for crimping a stent to aballoon includes the steps of i. elevating the temperature of the stent;ii. pre-crimping the stent including reducing the stent diameter from afirst diameter to about a final, crimped diameter while the stent issupported on a mandrel within a crimp head, wherein the stenttemperature has the elevated temperature while the diameter is beingreduced to about the final crimped diameter; iii. removing the stent andmandrel from the crimp head following the pre-crimping step and placingthe stent on a balloon catheter to assemble a stent-catheter assembly, aballoon of the balloon catheter capable of being pressurized through aproximal end of an inflation lumen of the balloon catheter; vi. placinga protective sheath over the stent, the protective sheath having aradial stiffness and an inner diameter that is about 20-30% greater thanthe stent outer diameter after step ii; v. placing the stent-catheterassembly within the crimp head and increasing the stent temperature tothe elevated temperature; vi. while the stent has the elevatedtemperature, coupling the stent to the balloon including the steps of(a) pressurizing the balloon via the inflation lumen while thestent-catheter assembly is within the crimp head, wherein the balloonpressure is maintained at a maximum pressure for a predetermined timeperiod and the stent is restrained from expanding beyond about 20-30% ofits diameter by the protective sheath, and (b) following step (a), whilemaintaining the elevated temperature and balloon pressure reducing thediameter of the stent to a third diameter, less than about the finalcrimped diameter using the crimp head; and vii. removing thestent-catheter assembly from the crimp head.

INCORPORATION BY REFERENCE

All publications and patent applications mentioned in this specificationare herein incorporated by reference to the same extent as if eachindividual publication or patent application was specifically andindividually indicated to be incorporated by reference, and as if eachsaid individual publication or patent application was fully set forth,including any figures, herein.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a plot showing temperature and stent outer diameter versestime for a prior art process. This process may be practiced inaccordance with the principles outlined in U.S. Pat. No. 7,763,198.

FIG. 1B is a plot showing a process according to the disclosure. As canbe readily discerned from a comparison between FIGS. 1A and 1B, theprocessing time for arriving at the final crimp diameter and desireddislodgment force is reduced by about 70%.

DETAILED DESCRIPTION OF EMBODIMENTS

For purposes of this disclosure, a “stent” means an open-walled tubularbody of interconnected, spaced-apart struts with gaps between adjacentstent struts. The struts may form rings having a serpentine wave patternof opposed turns and which are longitudinally spaced apart and connectedby links. The stent, when crimped to a balloon undergoes a process ofplastic deformation from a starting or manufactured diameter to a finalor crimped diameter. The stent is expanded to a deployed diameter bybeing plastically deformed by expansion of the balloon.

A stent having a pattern as described in U.S. Pat. No. 6,312,459 or U.S.Pat. No. 179,867 may have a starting, or manufactured outer surfacediameter of 0.07 in. The stent is made from a metal or metal alloy. Thestent may be crimped to a non-compliant balloon made from PEBAXmaterial. When deployed the stent has a nominal 3 mm (0.118 in) outerdiameter and 18 mm (0.708 in) length. For purposes of this disclosure,this stent will be referred to as the 3018 stent, or “the stent”,however, it will be appreciated that the principles discussed are notlimited to only this stent or stents of this size or design. The targetfinal crimped diameter for the stent is about 0.04 in. During the entireprocess—initial crimp, balloon inflation, final crimp and leak test—thestent is contained within a TEFLON or other suitable polymeric sheath,which protects the surface of the stent, particularly the drug-polymercoating from damage when coming into contact with metal crimper blades.For a 3.00 mm deployed diameter stent, e.g., the 3018 stent, and 0.04 incrimped diameter a sheath is preferably chosen having an inner diameterof about 0.052 in. Following the leak test the sheath may be peeled awayfrom the outer surface of the stent.

FIG. 1A shows processing time verses temperature and pressure values fora prior art crimping process similar to a process described in U.S. Pat.No. 7,763,198. In stage 1 of this process, the stent is placed within acrimper head having a temperature of about 70 degrees Fahrenheit and thediameter is reduced down to about 0.04 in. following a dwell period ofabout 1 minute the stent is removed from the crimper and placed on aballoon of a balloon catheter then re-inserted into the split molddevice described in U.S. Pat. No. 7,763,198. The temperature is raisedto a maximum of about 170 degrees Fahrenheit and pressure is raisedwhile the stent is held within the split mold, which restrains outerdiameter movement of the stent to about 0.048 in. After a period ofabout 185 seconds within the split mold the stent and balloon areremoved from the split mold then placed back within a crimper for are-crimp of the stent to the balloon. During this re-crimp period thestent is raised to a temperature of about 130 degrees Fahrenheit and thecrimper's iris moved to 0.03 in, which reduces the stent diameter toabout 0.03 in. After an additional dwell of about 40 seconds at 130degrees Fahrenheit the crimped stent and balloon are removed from thecrimper and a leak test performed. The leak test checks for any damageto the balloon. A leak test maintains the stent diameter at about the0.04 in profile while the balloon pressure is inflated, e.g., to about300 psi, and held at that pressure for about 60 seconds. The balloonpressure is monitored during this 60 second period to determine whetherthere is any pressure drop (indicating possible balloon damage).

The process just described is time consuming. Additionally, it isdesirable to increase the dislodgment force beyond that which ispossible when using the process according to FIG. 1A. For these andother reasons, which become apparent from the discussion that follows,the inventors were able to improve upon the process summarized above. Itwas discovered, unexpectedly that during the course of reducing thelength time needed for the crimping process, not only was there asignificant reduction in processing time, but it was also found that thestent dislodgment force could be increased significantly when utilizingthe processes according to the disclosure.

The following discussion describes a process summarized in FIG. 1B. Ascan be readily appreciated from FIG. 1B the processing time has beenreduced from about 350 seconds to about 90 seconds. According to oneembodiment of a process corresponding to FIG. 1B, all stages of thecrimp process are performed using a single crimper device. The processof FIG. 1A has been performed using up to three devices: a firstcrimping device (pre-crimp), the split mold and a second crimping device(re-crimp). Notably, the dwell times have been reduced significantly.Additionally, the process seeks to maintain about a 170 degreeFahrenheit temperature for each stage, which is preferable as itobviates the need to constantly adjust the temperature settings betweeneach stage (as in the case of FIG. 1A). Also, by utilizing a singlecrimping head, it becomes possible to transition from the second stage(“S2”) to the third stage (“S3”) while maintaining a desired temperatureand/or balloon pressure. This later ability, it was found, can yieldincreased dislodgment force. In one example, the stent dislodgment forceusing the process of FIG. 1A was about 2.2 lbs, whereas the dislodgmentforce was about 2.5 lbs when using processes associated with FIG. 1B forthe same stent final and starting diameter and balloon properties. Inother examples the dislodgment force was found to increase by about 12%when processes associated with FIG. 1B were used.

The stent at 0.07 in outer surface diameter is placed on a 0.0336 inouter surface mandrel defining an initial crimped diameter for thestent. The stent-mandrel assembly are centered in an iris-type crimphead and the stent outer surface diameter reduced down from 0.07 in toabout 0.04 in. The diameter reduction from 0.07 in to 0.04 in occursover a period of about 10 seconds, or the blades of the crimpertranslate from the iris diameter of 0.07 in to an iris diameter of 0.04in at a rate of 0.3 in/sec. There is a 5 second dwell period before theiris is withdrawn from the stent surface. In another embodiment the rateof diameter reduction is about 0.05 in/sec to the 0.04 in outerdiameter, followed by a 5 second dwell time.

The stent, when initially at the 0.07 in outer surface diameter andwithin the crimper head has an average temperature of about 170 degreesFahrenheit. Over the second period for diameter reduction to 0.04 inouter surface diameter and dwell, the stent temperature is reduced,e.g., the heat source is discontinued once the diameter reductionbegins. The temperature is reduced when the stent is removed from thecrimper head (as discussed below). The stent average temperature reachesabout 70 degrees Fahrenheit. The temperature drop plotted in FIG. 1Bafter about 5 and 15 seconds reflects, therefore, the temperature dropof the stent after it is removed from the 170 degree heated crimperhead. Preferably, the crimper head is maintained at about 170 degreesfor steps S1, S2 and S3.

The heat transfer mechanism used to arrive at the 170 degree startingtemperature may be heated crimper blades to about this temperature,heated gas, a heated supporting metal mandrel supporting the stentwithin the crimp head, or a combination of the above. In a preferredembodiment the temperature is raised by only heating the blades of thecrimper. Thus, the stent temperature is raised to about 170 degreesFahrenheit by only the convected and radiated heat from the bladesforming the crimper iris.

After the stent diameter has been reduced to about 0.04 in the crimperjaws during stage S1, the stent is withdrawn from the heated crimperhead. The stent is then removed from the mandrel and placed on thedelivery system, i.e., a non-compliant, folded PEBAX balloon of aballoon catheter. The stent is aligned between balloon markers thenplaced back into the crimper head for the next stage (S2) of thecrimping process. A sheath is then placed over the stent to protect apolymer-drug coating on the stent from possible damage that might occurwhen the blades of the crimper come into contact with the stent. Thesheath size may be selected according to an inner diameter size definingthe maximum extent the stent will expand during stage S2 when theballoon pressure is increased. In a preferred embodiment, a TEFLONsheath having an inner diameter of about 0.052 in is used for the stenthaving the initial crimp diameter of about 0.042 in prior to S2.

The selection of the inner diameter of the protective sheath is believedto have an effect on the amount of desirable pillowing of the balloonbetween stent struts during S2. If the sheath diameter is too small, itis believed that less than a desirable amount of pillowing will occur asthe balloon is restrained from expanding; thereby preventing the balloonmaterial from extending between stent struts. If the sheath diameter istoo large, then the stent can expand too much or other problems canoccur during the subsequent stage S3. Either or both of displacement orshifting of the stent relative to the balloon occurs, i.e., shifting thestent's alignment with respect to the balloon markers, or there is lesspillowing of balloon material between struts since the balloon and stentcan more freely move outward relative to each other, rather than forcingballoon material between stent struts due to a radial restraint imposedby the inner sheath diameter. A protective sheath diameter should alsonot be made too large as this may cause the sheath to crumple or foldover itself rather than be compressed during the final crimp (S3). It isbelieved that, to produce the desirable results for a stent with the3018 stent dimensions, for example, the sheath inner diameter wasselected to be between about 0.046 to 0.056 in, or more narrowly betweenabout 0.0048 to 0.054 in for an initial crimp stent diameter of about0.042 in. In other embodiments the sheath inner diameter may be chosento be between about 15-30%, 20-30%, or 20-25% greater than an outerdiameter of a polymer-drug coated stent. Depending on the diameter ofthe balloon being processed, a range from about 0.038″ to about 0.080″is contemplated. For example, in the case of the 3018 stent the rangemay be between about 0.042″ to 0.065″.

The catheter's luer fitting is connected to a pressure source forsupplying inflation pressure to the balloon lumen while thestent-catheter assembly is disposed within the crimper head. Balloonpressure is used in combination with other parameters such as heat andtemperature during Stages S2 and S3 of the crimping process of FIG. 1Bto arrive at a desired retention force and outer profile.

For stage S2 the stent, aligned on the balloon, has a diameter of about0.04 in. or slightly higher (e.g., about 0.042 in) due to elastic recoilof the material when the crimper jaws or blades are withdrawn. Thestent-balloon assembly (stent and balloon within a protective sheath) isplaced back into the heated crimper. After a period of about 5-10seconds the stent again attains a temperature of about 170 degrees.Concurrently with the rise in temperature, pressure is supplied to theballoon lumen, which causes the balloon diameter and stent outer surfacediameter to increase according to the sheath size (as discussedearlier). In one example, the inflation causes the stent outer surfacediameter to increase from about 0.042 in to about 0.052 in. In otherembodiments the stent outer surface may be capable of increasing 25-40%,25-35%, or more narrowly 28-32% when the balloon is pressurized. Theballoon pressure may be increased to a peak pressure of about 300 psiduring this phase of the crimping process. In other embodiments, balloonpressure may be 150 psi or between 150-300 psi, which pressure may beselected based on the length of time for S2, e.g., for a lower pressurethe dwell period may be increased.

In another embodiment, pillowing may be controlled or enhanced by usingthe crimper jaws, rather than, or in addition to a selected sheath innerdiameter for enhancing pillowing. By selecting a sheath inner diameterof about, e.g., 0.052 in for the 3018 stent, and in addition (oralternatively) setting the crimper jaws at a limit compressive force(beyond which the blades deflect away), or fixed diameter or enforceddisplacement setting, the pillowing effect between stent and balloon maybe affected to improve results. In one embodiment, the crimper bladesare set to a low compressive force, in addition to the sheath beingpresent to improve thermal conductivity from the blades to the stent. Bydisposing blades to contact the sheath the stent temperature may be morequickly raised than the case where the blades are offset from thesheath. In another embodiment the crimper blades may be withdrawn at arate matching the approximate rate (or slightly slower) of diameterincrease of stent diameter without the blades applying a radialcompressive force.

The crimper blades may be set in position to form an iris diameter ofabout, or slightly larger than the sheath outer diameter, respectively,so that the stent outer surface diameter cannot exceed this diametereven when the sheath is stretched (for thin-walled sheaths) duringballoon expansion. Alternatively, the crimper blades may be programmedto apply a slight compressive force to the stent and sheath that isexceeded by the forces of the stent on the blades as the stent isexpanded by balloon pressure. By applying this additional compressiveload (beyond that imposed by the sheath on the stent, balloon pillowingmay be further enhanced. In some embodiments a limit of 0.052 in maximumouter surface diameter reached by the stent may be achieved by eitherimposing an enforced maximum displacement (fixed displacement) by fixingthe iris at about the sheath outer diameter or slightly larger, or afixed force imposed by the crimper, which is overcome by balloonpressure over the S2 period so that at the end of the pressurizationperiod the stent diameter is at about 0.052 in.

In a preferred embodiment, a sheath having an inner diameter of about0.052 in for an about 0.042 in crimped stent profile is used to restrainoutward movement during stage S2. During S2 the stent outer diameterincreases from about 0.042 in about 0.052 in or to a diameter aboutequal to the sheath inner diameter. According to the disclosure, duringS2 the stent outer diameter may be increased by about 15-30% or morenarrowly about 20-25% and still more narrowly to about 22-24% during S2to achieve a desired amount of pillowing before transitioning to stageS3. The duration of S2 may be about 30 seconds for these ranges ofdiameter increase at a temperature of 170 degrees and pressure of about300 psi.

As mentioned above, stage S2, the balloon pressurization period, isintended for increasing or encouraging a pillowing effect between stentand balloon. “Pillowing effect” means the balloon material extendingbetween and through gaps in stent struts as balloon pressure isincreased under a restraint, i.e., a protective sheath inner diametersized according to the stent outer diameter. Pillowing facilitates theinterlocking of balloon material with stent struts. The temperature isabout 170 degrees Fahrenheit, which can facilitate the pillowing effectas the balloon material, being expanded by the lumen pressure and itssurface and stent surface having a raised temperature, can better extendbetween the stent struts. Once located between stent struts, the stentdislodgment force is increased significantly over a stent that reliesonly on friction between the crimped stent and balloon. Preferably, theballoon used does not contain ridges or protrusions to facilitate stentretention. Rather, results were achieved with a PEBAX balloon having arelatively smooth surface.

The stent and balloon are kept within the crimper head as the processtransitions from Stage S2 to Stage S3 in FIG. 1B. During Stage S3 thestent diameter is reduced down to about the 0.04 in diameter again. Aballoon pressure, e.g., 300 psi, and temperature of 170 degreesFahrenheit are maintained during the diameter reduction from about the0.052 in following Stage 2, and/or during the dwell period of about 3seconds for S3. For S3 there may be successive crimp, dwell and releaseintervals for purposes of working metal to reduce recoil when the jawsare removed. Additionally, it was found that this cycling between crimpdiameters (e.g., applying then releasing crimp jaws) also increased thedislodgment force. In one embodiment there are 7 periods where the stentis reduced in diameter, a dwell period follows, then a brief periodwhere the jaws are released or moved to a larger diameter, e.g., from0.03 in to 0.03 in. For S3 the crimp diameter may be enforced to areduced diameter by the crimper blades, then allowed to recoil to up toa final crimp diameter.

Tables 1, 2 and 3 below provide the parameters for stent crimping forsome of the embodiments discussed above. The target outer diameter forthe final crimped size was 0.04 in for the 3018 stent in Tables 1, 2 and3 following the leak test. After the leak test the protective sheath isremoved.

Under column “Speed (in/sec)” the values of 0.05 in/sec and 0.300 in/secare given. In some embodiments the rate at which the crimper blades arebrought down on the stent to decrease its diameter, or rate at which theballoon is inflated can be altered to affect the amount of stentretention to the balloon. In the embodiments the rate of balloonexpansion, and/or crimping rate may be between 0.05 and 0.300 in/sec.

Examples 1 and 2, summarized under Tables 1 and 2, respectively, are thesame, except that in Example 1 balloon pressure is applied only duringthe dwell periods of S3. The crimp head speed is 0.05 in/sec for Example1 and 0.300 in/sec for Example 2. Balloon pressure is applied during thediameter reduction and dwell periods of S3 in Example 2. Pressure wasapplied during all traverse times including from 51 to S2 in additionfrom s2 to s3 for Example 2 (as well as Examples 3 and 4, below). Inother embodiments, it is contemplated that results may be improvedfurther by applying balloon pressure (constant or varying) during alltraverse times, including during each step of a multi-stage S3 process(e.g., Examples 3 and 4). The resulting dislodgment force was greaterfor Example 2 (1.0 lbs compared with 1.4 lbs, or about 40% increase,over Example 1).

TABLE 1 Example 1 crimping parameters (3 × 18 metal stent) Diam- BalloonTemp eter Speed Dwell Pressure mandrel (deg. Stage (in) (in/sec) (sec)(psi) size (in) F.) S1 .0336 .05 5 0 .036 170 pressurize S2 .070 .05 30300 balloon S3 .040 .05 3 300 during dwell only

TABLE 2 Example 2 crimping parameters (3 × 18 metal stent) Diam- BalloonTemp eter Speed Dwell Pressure mandrel (deg. Stage (in) (in/sec) (sec)(psi) size (in) F.) S1 .0336 .300 5 0 .036 170 pressurize S2 .070 .30030 300 balloon S3 .040 .300 3 300 during dwell and diameter reduction

Examples 1 and 2 were compared to a crimping process in which no balloonpressure was applied during Stage 3. It was found that the dislodgmentforce increased by about 0.4 lb when balloon pressure was present duringStage 3. The final outer diameter increased by about 0.003 mm whenballoon pressure was applied during Stage 3.

Example 3 shows multiple final crimp cycles applied during stage S3. Inthis example, several cycles of crimp, dwell and release under balloonpressure were applied. The period where the crimp blades are withdrawnare indicated by the diameter 0.3 in. As shown, following a 3 seconddwell the crimp head force is relieved and 300 psi reduced to about 0psi for about 0.1 second (essentially, the pressure is relieved and headwithdrawn for only a very brief period), then the crimp head appliedagain and balloon pressure of 300 psi re-applied. After the initialdiameter reduction to 0.04 mm, the same process of crimp, dwell andrelease are applied to the 3018 stent, as shown.

TABLE 3 Example 3 crimping parameters (3 × 18 stent) Balloon Speed DwellPressure mandrel Temp Stage Diameter (in) (in/sec) (sec) (psi) size (in)(deg. F.) S1 0.0336 0.100 5 0 .036 170 S2 0.070 0.100 30 300 S3 0.0400.300 3 300 S3 0.300 0.100 0.1 0 S3 0.040 0.300 3 300 S3 0.300 0.100 0.10 S3 0.040 0.300 3 300 S3 0.300 0.100 0.1 0

The Example 1 crimping process was compared to the Example 3 crimpingprocess. It was found that when the crimping process of Example 3 isused, the crimp profile may be reduced to about 0.0388 in verses about0.0398 and the dislodgment force increased over the Example 1 process.Thus, using the Example 3 process about the same final crimp diameter,or slightly less, was achieved while, at the same time, the dislodgmentforce was increased.

In Example 4, the crimp head is not opened and closed as in Example 3but instead, moved between a 0.04 in iris diameter to 0.03 in irisdiameter. This additional example is summarized in TABLE 4, below.

TABLE 4 Example 4 crimping parameters (3 × 18 stent) Balloon Speed DwellPressure mandrel Temp Stage Diameter (in) (in/sec) (sec) (psi) size (in)(deg. F.) S1 0.0336 0.100 5 0 .036 170 S2 0.070 0.100 30 300 S3 0.0300.300 3 300 S3 0.040 0.100 0.1 0 S3 0.030 0.300 3 300 S3 0.040 0.100 0.10 S3 0.030 0.300 3 300 S3 0.040 0.100 0.1 0

For Example 4 the dwell period takes place while the crimp head iris isfixed at 0.04 in, i.e., the final crimp diameter, followed by a further25% diameter reduction for a brief period, followed by a return to the0.04 in final diameter for an additional 3 second dwell. During thediameter reduction to 0.03 in the balloon pressure is 300 psi, and thenthe balloon pressure reduced when the iris is again moved from 0.03 into 0.04 in.

Comparing the balloon pressure periods for Example 3 verses Example 4,in Example 3 balloon pressure is applied when the 0.04 in diameter isenforced by the crimp head, i.e., when the diameter is reduced (if any)from the unload diameter to the 0.04 in diameter. During the dwellperiod the stent is not loaded by the crimp head, nor is balloonpressure applied (a period of about 0.1 seconds). In Example 4, balloonpressure is applied when the diameter is reduced from 0.04 in to 0.03in. Balloon pressure is relieved during the brief dwell period when thestent is allowed to expand up to about 0.04 in.

The cycles performed during Stage 3 according to Examples 3 and 4 arebelieved beneficial for the following reasons. First, by moving thestent diameter repeatedly from the unloaded or larger diameter, e.g.,0.04 as in Example 4, to the reduced diameter the material is worked toreduce recoil when the stent is finally removed from the crimper.Additionally, by moving between the two diameters while increasing andrelieving pressure the balloon material can further nestle in betweenstent struts to increase the dislodgment force. Notably, it was foundthat the desired dislodgment force could be obtained by the cyclingprocess adopted in Examples 3 and 4 without requiring a lengthy dwelltime as in the prior art process, or be reducing the profile diameterbeyond the desired amount. Thus, the desired dislodgment force could beobtained with a cycling process replacing the lengthy dwell periodpreviously used to increase the dislodgment force, while maintaining thedesired profile.

As mentioned earlier, the above mentioned processes, e.g., Example 3,are completed in substantially less time than previously thoughtpossible. Prior to the invention, it was believed substantially moredwell time was needed for each stage to reduce recoil in the stent andpermit pillowing to take effect. FIG. 1 shows a comparison of the timeduration for a three stage process according to the invention, comparedto the prior art three stage process. Plotted for each of the twoprocesses are stent outer diameter (vertical bars) and temperature (linegraph) verses time.

As can be appreciated from FIG. 1, the pre crimp processing time withinthe crimp head was reduced from about 70 seconds to about 25 second. TheS2 or pillowing stage was reduced from about 180 seconds to 25 seconds.Finally, the S3 or final crimp/press stage was reduced from about 50seconds to about 10 seconds. Thus, the overall process time for crimpingthe 3018 stent was reduced from about 350 seconds to about 60 seconds(not including leak test dwell period).

The processes of Examples 2, 3 and 4 each include maintaining pressureand temperature as the process transitions from S2 to S3, i.e., diameterreduction from the about 0.02 in diameter to 0.04 in or 0.03 in.Surprisingly, by maintaining pressure during this phase of the processthere was a noticeable increase in the dislodgment force without anysignificant increase or change in profile diameter or deleterious effecton the stent deployment or balloon integrity. While not wishing to betied to any particular theory, it is believed that the dislodgment orretention force increased by maintaining pressure during the S2 to S3diameter reduction (as opposed to not applying balloon pressure as inExample 1) because the presence of balloon pressure helped to maintainthe presence of balloon material between stent struts that was formedduring S2. Without this balloon pressure being applied, it is believedthat the about 25% to about 40% diameter reduction of the stent duringthe S2 to S3 transition had caused balloon material to be pushed orforced out from between stent struts as the spacing between the strutsis reduced.

The examples given above refer to dimensions for a 3018 stent diameterand desired crimped profile for this stent. The principles expressed,however, are applicable to stents of different sizes. Accordingly, thedisclosure should not be limited to a stent having a particular crimpedprofile or deployed diameter, such as the 3018 stent. Moreover, wherethere is recitation of “the stent”, as opposed to “a stent”, it would beincorrect to conclude that by use of the definite article “the” thediscussion is necessarily referring to only the 3018 stent or only thosestents having similar dimensions to that of the 3018 stent. One ofordinary skill will recognize that the principles discussed herein maybe applied to stents other than the 3018 stent or similar stents.

While particular embodiments of the present invention have been shownand described, it will be obvious to those skilled in the art thatchanges and modifications can be made without departing from thisinvention in its broader aspects. Therefore, the appended claims are toencompass within their scope all such changes and modifications as fallwithin the true spirit and scope of this invention.

1. A method for crimping a stent to a balloon, comprising: i. elevatingthe temperature of the stent; ii. pre-crimping the stent includingreducing the stent diameter to a first diameter while the stent issupported on a mandrel within a crimp head, wherein the stent has afirst elevated temperature while the diameter is being reduced to thefirst diameter; iii. removing the stent and mandrel from the crimp headfollowing the pre-crimping step and placing the stent on a ballooncatheter to assemble a stent-catheter assembly, a balloon of the ballooncatheter capable of being pressurized through a proximal end of aninflation lumen of the balloon catheter; iv. placing the stent-catheterassembly within the crimp head and increasing the stent temperature to asecond elevated temperature, while the stent has the second elevatedtemperature, pressurizing the balloon via the inflation lumen while thestent-catheter assembly is within the crimp head, wherein the stentdiameter is restrained to expand to a second diameter up to about 25-30%greater than the first diameter when the balloon is pressurized to causeballoon material to extend between stent struts; v. following step iv,pressing the stent into the balloon, the stent having a third elevatedtemperature, step v including reducing the stent diameter using thecrimp head from about the second diameter to about a final diameterwhile maintaining the balloon pressure wherein the diameter is reducedby about 25% to 40% from the second diameter while balloon pressure ismaintained; and vi. removing the stent-catheter assembly from the crimphead.
 2. The method of claim 1, wherein step iii includes placing asheath having an inner diameter of about 25% greater than the stentfirst diameter over the stent to protect a coating on the stent, whereinthe sheath has a radial stiffness such that the presence of the sheathover the stent provides the up to about 25-30% greater than the firstdiameter restraint on stent expansion during step iv.
 3. The method ofclaim 1, wherein the first diameter is about the same as the finaldiameter.
 4. The method of claim 1, wherein the first, second and thirdelevated temperatures are the same.
 5. The method of claim 1, whereinstep v further includes steps (a) through (e): (a) reducing the stentdiameter to about the final crimp diameter while maintaining the balloonpressure; (b) maintaining the balloon pressure for a dwell period whilethe crimp head is at the about the final crimped diameter; (c) afterstep (b), reducing the balloon pressure and withdrawing the crimp headfrom the stent to thereby allow the stent to recoil; (d) moving thecrimp head back to about the final crimp diameter following step (c);and (e) repeating steps (b) through (d) more than twice.
 6. The methodof claim 5, wherein the time duration in (c) is about 0.1 seconds, theballoon pressure for step (a) is about 300 psi and the balloon pressureis allowed to drop to a value attainable after 0.1 seconds before againincreasing pressure and re-applying the crimp head to the stentaccording to step (d).
 7. The method of claim 1, wherein step v furtherincludes steps (a) through (e): (a) reducing the stent diameter to athird diameter, less than the final crimp diameter while maintaining theballoon pressure; (b) maintaining the balloon pressure for a dwellperiod while the crimp head is at the third diameter; (c) after step(b), reducing the balloon pressure, followed by increasing the crimphead diameter to allow the stent to recoil from the third diameter to alarger diameter; (d) increasing the balloon pressure and moving thecrimp head back to about the third diameter following step (c); and (e)repeating steps (b) through (d) more than twice.
 8. The method of claim7, wherein the third diameter is between about 20-40% less than thefinal crimp diameter.
 9. The method of claim 8, wherein the timeduration in (c) is about 0.1 seconds, the balloon pressure for step (a)is about 300 psi and the balloon pressure is allowed to drop to a valueattainable after 0.1 seconds before again increasing pressure andre-applying the crimp head to the stent according to step (d).
 10. Amethod for crimping a stent to a balloon, comprising: i. elevating thetemperature of the stent; ii. pre-crimping the stent including reducingthe stent diameter from a first diameter o about a final, crimpeddiameter while the stent is supported on a mandrel within a crimp head,wherein the stent temperature has the elevated temperature while thediameter is being reduced to about the final crimped diameter; iii.removing the stent and mandrel from the crimp head following thepre-crimping step and placing the stent on a balloon catheter toassemble a stent-catheter assembly, a balloon of the balloon cathetercapable of being pressurized through a proximal end of an inflationlumen of the balloon catheter; vi. placing a protective sheath over thestent, the protective sheath having a radial stiffness and an innerdiameter that is about 20-30% greater than the stent outer diameterafter step ii. v. placing the stent-catheter assembly within the crimphead and increasing the stent temperature to the elevated temperature;vi. while the stent has the elevated temperature, coupling the stent tothe balloon including (a) pressurizing the balloon via the inflationlumen while the stent-catheter assembly is within the crimp head,wherein the balloon pressure is maintained at a maximum pressure for apredetermined time period and the stent is restrained from expandingbeyond about 20-30% of its diameter by the protective sheath, (b)following step (a), while maintaining the elevated temperature andballoon pressure reducing the diameter of the stent to a third diameter,less than about the final crimped diameter using the crimp head; andvii. removing the stent-catheter assembly from the crimp head.
 11. Themethod of claim 10, step (b) further including the step of reducing thediameter of the stent to the third diameter while maintaining about thesame balloon pressure as in step (a), followed by withdrawing the crimphead from the stent and reducing balloon pressure for about 0.1 secondsthen again reducing the stent to the third diameter at the balloonpressure, and repeating this step a plurality of times to thereby cyclethe stent with balloon material to further increase a stent dislodgmentforce.
 12. The method of claim 11, wherein step (b) further includesreducing the stent diameter down by about 40% simultaneously with thestent having the elevated temperature and the balloon applying about a300 psi pressure to the stent inner surface to thereby maintain apresence of balloon material between stent struts following step (a).